Living inside the box: environmental effects on mouse models of human disease.
The authors thank Dr Gavin Jarvis for pointing out the similarities between experimental heterogenization and population pharmacokinetic strategies, and Dr Lillian Garrett for stimulating discussions on mouse behavior. We thank Profs. Lenny Schultz and Steve Brown, and Dr Bonnie Lyons for helpful comments on the manuscript.
The impact of the laboratory environment on animal models of human disease, particularly the mouse, has recently come under intense scrutiny regarding both the reproducibility of such environments and their ability to accurately recapitulate elements of human environmental conditions. One common objection to the use of mice in highly controlled facilities is that humans live in much more diverse and stressful environments, which affects the expression and characteristics of disease phenotypes. In this Special Article, we review some of the known effects of the laboratory environment on mouse phenotypes and compare them with environmental effects on humans that modify phenotypes or, in some cases, have driven genetic adaptation. We conclude that the 'boxes' inhabited by mice and humans have much in common, but that, when attempting to tease out the effects of environment on phenotype, a controlled and, importantly, well-characterized environment is essential.